Antibody-dependent cellular cytotoxicity (ADCC) in COG ANBL0032: A phase III randomized trial of chimeric anti-GD2 and GM-CSF/IL2 in high risk neuroblastoma following myeloablative therapy and autologous stem cell transplant (ASCT)

Abstract

2582 Background: ADCC plays an important role in the efficacy of anti-cancer monoclonal antibody therapy. We monitored ADCC activities of neuroblastoma patients enrolled on COG ANBL0032. Methods: High risk neuroblastoma patients who achieved a complete or very good partial response after induction therapy, myeloablation with carboplatin + etoposide + melphalan, ASCT, and local radiation according to COGA3973, were eligible for this study. After engraftment, they were randomized to 13-cis-retinoic acid (RA) x 6 courses or RA + immunotherapy with 5 courses of Ch14.18 and alternating cycles of GM-csf and IL2. Results: So far, 27 patients have been evaluated before treatment on day 76 ± 9 (62∼93) post-ASCT. The mononuclear cells of all 27 patients displayed ADCC which averaged 43.2 ± 28.3 LU20 (11.7∼138). Granulocytes of all 23 patients evaluated pre-treatment also showed ADCC with an average of 18.7 ± 17.9 LU20(3.4∼67.5). ADCC of both cell types were significantly less than that observed for 5 normal donors who had a mean of 145.7 ± 58.3 LU20 (P=0.001) for mononuclear cells and 26.7 ± 7.1 (P=0.0168) for granulocytes. ADCC mediated by both cell types in patients did not change significantly subsequently: before 4th course of RA/ immunotherapy on day 163, and before last course of RA/ immunotherapy on day 196. Although impaired chemotaxis of granulocytes has been reported during IL-2 therapy, we found no significant changes in granulocyte mediated ADCC, right before and after ch14.18 + IL2. Conclusions: These findings suggest that ADCC mediated by mononuclear cells and granulocytes are present shortly after ASCT and persist throughout the course of immunotherapy, albeit at lower levels than normal controls, which is consistent with the reported decreased ADCC in cancer patients. The preliminary findings so far indicated that there is residual ADCC following ASCT, which may allow the monoclonal antibody to be efficacious. No significant financial relationships to disclose.